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01-03-2012 | Original Article

Cytokines and sudden infant death

Authors: Mechtild M. T. Vennemann, Brigitte Loddenkötter, Tony Fracasso, Edwin A. Mitchell, Annette S. Debertin, Klaus P. Larsch, Jan P. Sperhake, Bernd Brinkmann, Cristina Sauerland, Monika Lindemann, Thomas Bajanowski

Published in: International Journal of Legal Medicine | Issue 2/2012

Abstract

Background

It has been hypothesised that inflammatory reactions could play an important role in the pathway(s) leading to sudden and unexpected death in infancy. On a molecular level, these reactions are regulated by various cytokines.

Methods

To characterise the role of IL-1ß, IL-6 and TNFα more precisely, the concentrations of these cytokines were determined quantitatively using specific ELISA techniques in serum and cerebrospinal fluid (CSF) in 119 cases of sudden infant death. The infants were grouped into four categories (SIDS, SIDS with infection, natural death due to infection and unnatural death).

Results

A good correlation was found between CSF and serum for IL-6 (Spearman correlation coefficients (SCC), 0.73) and also for TNFα (SCC, 0.57), although the CSF concentrations were lower than that from the serum. There were no significant differences between the categories of death for any of the serum or CSF cytokines. Compared with normal values, increased serum concentrations of IL-1ß, IL-6 and TNFα were found in 70%, 69% and 38% of the cases respectively, indicating possible agonal or post-mortem changes of cytokine concentrations. In three cases very high cytokine concentrations were found (mainly for IL-6). This may have contributed to the mechanism of death (cytokine storm) in two of the cases.

Conclusions

In a small group of patients, very high cytokine concentrations are a possible explanation for the cause of death (“cytokine storm”).

Guntheroth WG (1989) Interleukin-1 as intermediary causing prolonged sleep apnea and SIDS during respiratory infections. Med Hypotheses 28:121–123PubMedCrossRef

Stoltenberg L, Vege A, Opdal SH, Saugstad OD, Rognum TO (1995) Does immunostimulation play a role in SIDS? In: Rognum TO (ed) Sudden infant death syndrome. New trends in the nineties. Scandinavian University Press, Oslo pp. 179–181

Vege A, Rognum TO, Aasen AO, Saugstad OD (1998) Are elevated cerebrospinal fluid levels of IL-6 in sudden unexplained deaths, infectious deaths and deaths due to heart/lung disease in infants and children due to hypoxia? Acta Paediatr 87:819–824PubMedCrossRef

Blackwell CC, Moscovis SM, Gordon AE, Al Madani OM, Hall ST, Gleeson M et al (2005) Cytokine responses and sudden infant death syndrome: genetic, developmental, and environmental risk factors. J Leukoc Biol 78:1242–1254PubMedCrossRef

Rivest S, Lacroix S, Vallieres L, Nadeau S, Zhang J, Laflamme N (2000) How the blood talks to the brain parenchyma and the paraventricular nucleus of the hypothalamus during systemic inflammatory and infectious stimuli. Proc Soc Exp Biol Med 223:22–38PubMedCrossRef

Dinarello CA (2011) Blocking interleukin-1beta in acute and chronic autoinflammatory diseases. J Intern Med 269:16–28PubMedCrossRef

Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F (2003) Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J 374:1–20PubMedCrossRef

Jones SA (2005) Directing transition from innate to acquired immunity: defining a role for IL-6. J Immunol 175:3463–3468PubMed

Fischer CP (2006) Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Immunol Rev 12:6–33PubMed

10.

Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501PubMedCrossRef

11.

Old LJ (1985) Tumor necrosis factor (TNF). Science 230:630–632PubMedCrossRef

12.

Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differ 10:45–65PubMedCrossRef

13.

Findeisen M, Vennemann M, Brinkmann B, Ortmann C, Rose I, Kopcke W et al (2004) German study on sudden infant death (GeSID): design, epidemiological and pathological profile. Int J Legal Med 118:163–169PubMedCrossRef

14.

Krous HF, Beckwith JB, Byard RW, Rognum TO, Bajanowski T, Corey T et al (2004) Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics 114:234–238PubMedCrossRef

15.

Berdat PA, Wehrle TJ, Kung A, Achermann F, Sutter M, Carrel TP et al (2003) Age-specific analysis of normal cytokine levels in healthy infants. Clin Chem Lab Med 41:1335–1339PubMedCrossRef

16.

Laboratoriumsmedizin Dortmund. Available at http://www.labmed.de/de/de/laboratoriumsmedizin_dortmund-981.html. Accessed 13 July 2011.

17.

Dinarello CA (1988) New concepts on the pathogenesis of fever. Rev Infect Dis 10:168–179PubMedCrossRef

18.

Kunkel SL, Streiter RM (1990) Cytokine networking in lung inflammation. Hosp Pract (Off Ed) 15:63–76

19.

Sayers NM, Drucker DB, Grencis RK (1995) Cytokines may give insight into mechanisms of death in sudden infant death syndrome. Med Hypotheses 45:369–374PubMedCrossRef

20.

Reid GM (2001) Sudden infant death syndrome. Part 2: the response of the reticuloendothelial system to hypoxemia and infection. Med Hypotheses 57:1–5PubMedCrossRef

21.

Goldwater PN (2004) SIDS pathogenesis: pathological findings indicate infection and inflammatory responses are involved. FEMS Immunol Med Microbiol 42:11–20PubMedCrossRef

22.

Moscovis SM, Gordon AE, Al Madani OM, Gleeson M, Scott RJ, Roberts-Thomson J et al (2004) Interleukin-10 and sudden infant death syndrome. FEMS Immunol Med Microbiol 42:130–138PubMedCrossRef

23.

Rognum IJ, Haynes RL, Vege A, Yang M, Rognum TO, Kinney HC (2009) Interleukin-6 and the serotonergic system of the medulla oblongata in the sudden infant death syndrome. Acta Neuropathol 118:519–530PubMedCrossRef

24.

Tsokos M, Reichelt U, Jung R, Nierhaus A, Püschel K (2001) Interleukin-6 and C-reactive protein serum levels in sepsis-related fatalities during the early postmortem period. Forensic Sci Int 119:47–56PubMedCrossRef

25.

Mimasaka S (2002) Postmortem cytokine levels and the cause of death. Tohoku J Exp Med 197:145–150PubMedCrossRef

Title: Cytokines and sudden infant death
Authors: Mechtild M. T. Vennemann
Brigitte Loddenkötter
Tony Fracasso
Edwin A. Mitchell
Annette S. Debertin
Klaus P. Larsch
Jan P. Sperhake
Bernd Brinkmann
Cristina Sauerland
Monika Lindemann
Thomas Bajanowski
Publication date: 01-03-2012
Publisher: Springer-Verlag
Published in: International Journal of Legal Medicine / Issue 2/2012
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-011-0638-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cytokines and sudden infant death

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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